Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 13 de 13
Filtrar
Mais filtros








Base de dados
Intervalo de ano de publicação
1.
J Neurodev Disord ; 16(1): 19, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637762

RESUMO

BACKGROUND: Congenital cytomegalovirus (cCMV) is the most common congenital viral infection in the United States. Symptomatic infections can cause severe hearing loss and neurological disability, although ~ 90% of cCMV infections are asymptomatic at birth. Despite its prevalence, the long-term neurobehavioral risks of asymptomatic cCMV infections are not fully understood. The objective of this work was to evaluate for potential long-term neurobehavioral sequelae in infants with asymptomatic cCMV. METHODS: Infants with cCMV were identified from a universal newborn cCMV screening study in a metropolitan area in the midwestern United States. Asymptomatic infants with cCMV were enrolled in a longitudinal neurodevelopmental study (N = 29). Age- and sex-matched healthy control infants (N = 193) were identified from the Baby Connectome Project (BCP), a longitudinal study of brain and behavioral development. The BCP sample supplemented an additional group of healthy control infants (N = 30), recruited from the same participant registry as the BCP specifically for comparison with infants with asymptomatic cCMV. Neurobehavioral assessments and parent questionnaires, including the Mullen Scales of Early Learning, the Repetitive Behavior Scales for Early Childhood (RBS-EC), and the Infant Toddler Social Emotional Assessment (ITSEA) were administered at 12 months of age. Neurobehavioral scores were compared between infants with asymptomatic cCMV and all identified healthy control infants. RESULTS: Infants with asymptomatic cCMV performed equivalently compared to healthy control infants on the neurobehavioral measures tested at 12 months of age. CONCLUSIONS: These results indicate that at 12 months of age, infants with asymptomatic cCMV are not statistically different from controls in a number of neurobehavioral domains. Although follow-up is ongoing, these observations provide reassurance about neurobehavioral outcomes for infants with asymptomatic cCMV and inform the ongoing discussion around universal screening. Additional follow-up will be necessary to understand the longer-term outcomes of these children.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Recém-Nascido , Lactente , Humanos , Pré-Escolar , Estudos Longitudinais , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/diagnóstico , Triagem Neonatal/métodos , Encéfalo
2.
Children (Basel) ; 10(6)2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37371237

RESUMO

Hypoxic ischemic encephalopathy (HIE) remains a significant cause of disability despite treatment with therapeutic hypothermia (TH). Many survive with more subtle deficits that affect daily functioning and school performance. We have previously shown an early indication of hippocampal changes in infants with HIE despite TH. The aim of this study was to evaluate the hippocampal volume via MRI and memory function at 5 years of age. A cohort of children followed from birth returned for a 5-year follow-up (n = 10 HIE treated with TH, n = 8 healthy controls). The children underwent brain MRI and neurodevelopmental testing to assess their brain volume, general development, and memory function. Children with HIE had smaller hippocampal volumes than the controls despite no differences in the total brain volume (p = 0.02). Children with HIE generally scored within the average range on developmental testing. Though there was no difference in the memory scores between these groups, there was a positive within-group correlation between the hippocampal volume and memory scores in children with HIE (sentence recall r = 0.66, p = 0.038). There was no relationship between newborn memory function and 5-year hippocampal size. Children with HIE treated with TH experienced significant and lasting changes to the hippocampus despite improvements in survival and severe disability. Future studies should target diminishing injury to the hippocampus to improve overall outcomes.

3.
Epilepsy Behav ; 144: 109254, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37209552

RESUMO

INTRODUCTION: Self-limited epilepsy with centrotemporal spikes is a transient developmental epilepsy with a seizure onset zone localized to the centrotemporal cortex that commonly impacts aspects of language function. To better understand the relationship between these anatomical findings and symptoms, we characterized the language profile and white matter microstructural and macrostructural features in a cohort of children with SeLECTS. METHODS: Children with active SeLECTS (n = 13), resolved SeLECTS (n = 12), and controls (n = 17) underwent high-resolution MRIs including diffusion tensor imaging sequences and multiple standardized neuropsychological measures of language function. We identified the superficial white matter abutting the inferior rolandic cortex and superior temporal gyrus using a cortical parcellation atlas and derived the arcuate fasciculus connecting them using probabilistic tractography. We compared white matter microstructural characteristics (axial, radial and mean diffusivity, and fractional anisotropy) between groups in each region, and tested for linear relationships between diffusivity metrics in these regions and language scores on neuropsychological testing. RESULTS: We found significant differences in several language modalities in children with SeLECTS compared to controls. Children with SeLECTS performed worse on assessments of phonological awareness (p = 0.045) and verbal comprehension (p = 0.050). Reduced performance was more pronounced in children with active SeLECTS compared to controls, namely, phonological awareness (p = 0.028), verbal comprehension (p = 0.028), and verbal category fluency (p = 0.031), with trends toward worse performance also observed in verbal letter fluency (p = 0.052), and the expressive one-word picture vocabulary test (p = 0.068). Children with active SeLECTS perform worse than children with SeLECTS in remission on tests of verbal category fluency (p = 0.009), verbal letter fluency (p = 0.006), and the expressive one-word picture vocabulary test (p = 0.045). We also found abnormal superficial white matter microstructure in centrotemporal ROIs in children with SeLECTS, characterized by increased diffusivity and fractional anisotropy compared to controls (AD p = 0.014, RD p = 0.028, MD p = 0.020, and FA p = 0.024). Structural connectivity of the arcuate fasciculus connecting perisylvian cortical regions was lower in children with SeLECTS (p = 0.045), and in the arcuate fasciculus children with SeLECTS had increased diffusivity (AD p = 0.007, RD p = 0.006, MD p = 0.016), with no difference in fractional anisotropy (p = 0.22). However, linear tests comparing white matter microstructure in areas constituting language networks and language performance did not withstand correction for multiple comparisons in this sample, although a trend was seen between FA in the arcuate fasciculus and verbal category fluency (p = 0.047) and the expressive one-word picture vocabulary test (p = 0.036). CONCLUSION: We found impaired language development in children with SeLECTS, particularly in those with active SeLECTS, as well as abnormalities in the superficial centrotemporal white matter as well as the fibers connecting these regions, the arcuate fasciculus. Although relationships between language performance and white matter abnormalities did not pass correction for multiple comparisons, taken together, these results provide evidence of atypical white matter maturation in fibers involved in language processing, which may contribute to the aspects of language function that are commonly affected by the disorder.


Assuntos
Epilepsia Rolândica , Substância Branca , Humanos , Criança , Substância Branca/diagnóstico por imagem , Imagem de Tensor de Difusão , Epilepsia Rolândica/diagnóstico por imagem , Idioma , Imageamento por Ressonância Magnética , Anisotropia
4.
bioRxiv ; 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-36993540

RESUMO

Objectives: Brain segmentation of infant magnetic resonance (MR) images is vitally important in studying developmental mental health and disease. The infant brain undergoes many changes throughout the first years of postnatal life, making tissue segmentation difficult for most existing algorithms. Here, we introduce a deep neural network BIBSNet (Baby and Infant Brain Segmentation Neural Network), an open-source, community-driven model that relies on data augmentation and a large sample size of manually annotated images to facilitate the production of robust and generalizable brain segmentations. Experimental Design: Included in model training and testing were MR brain images on 84 participants with an age range of 0-8 months (median postmenstrual ages of 13.57 months). Using manually annotated real and synthetic segmentation images, the model was trained using a 10-fold cross-validation procedure. Testing occurred on MRI data processed with the DCAN labs infant-ABCD-BIDS processing pipeline using segmentations produced from gold standard manual annotation, joint-label fusion (JLF), and BIBSNet to assess model performance. Principal Observations: Using group analyses, results suggest that cortical metrics produced using BIBSNet segmentations outperforms JLF segmentations. Additionally, when analyzing individual differences, BIBSNet segmentations perform even better. Conclusions: BIBSNet segmentation shows marked improvement over JLF segmentations across all age groups analyzed. The BIBSNet model is 600x faster compared to JLF and can be easily included in other processing pipelines.

5.
Proc Mach Learn Res ; 172: 1075-1084, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36968615

RESUMO

Longitudinal studies of infants' brains are essential for research and clinical detection of neurodevelopmental disorders. However, for infant brain MRI scans, effective deep learning-based segmentation frameworks exist only within small age intervals due to the large image intensity and contrast changes that take place in the early postnatal stages of development. However, using different segmentation frameworks or models at different age intervals within the same longitudinal data set would cause segmentation inconsistencies and age-specific biases. Thus, an age-agnostic segmentation model for infants' brains is needed. In this paper, we present "Infant-SynthSeg", an extension of the contrast-agnostic SynthSeg segmentation framework applicable to MRI data of infants at ages within the first year of life. Our work mainly focuses on extending learning strategies related to synthetic data generation and augmentation, with the aim of creating a method that employs training data capturing features unique to infants' brains during this early-stage development. Comparison across different learning strategy settings, as well as a more-traditional contrast-aware deep learning model (nnU-net) are presented. Our experiments show that our trained Infant-SynthSeg models show consistently high segmentation performance on MRI scans of infant brains throughout the first year of life. Furthermore, as the model is trained on ground truth labels at different ages, even labels that are not present at certain ages (such as cerebellar white matter at 1 month) can be appropriately segmented via Infant-SynthSeg across the whole age range. Finally, while Infant-SynthSeg shows consistent segmentation performance across the first year of life, it is outperformed by age-specific deep learning models trained for a specific narrow age range.

6.
J Clin Neurophysiol ; 38(2): 112-123, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33661787

RESUMO

SUMMARY: High-density EEG (HD-EEG) recordings use a higher spatial sampling of scalp electrodes than a standard 10-20 low-density EEG montage. Although several studies have demonstrated improved localization of the epileptogenic cortex using HD-EEG, widespread implementation is impeded by cost, setup and interpretation time, and lack of specific or sufficient procedural billing codes. Despite these barriers, HD-EEG has been in use at several institutions for years. These centers have noted utility in a variety of clinical scenarios where increased spatial resolution from HD-EEG has been required, justifying the extra time and cost. We share select scenarios from several centers, using different recording techniques and software, where HD-EEG provided information above and beyond the standard low-density EEG. We include seven cases where HD-EEG contributed directly to current clinical care of epilepsy patients and highlight two novel techniques which suggest potential opportunities to improve future clinical care. Cases illustrate how HD-EEG allows clinicians to: case 1-lateralize falsely generalized interictal epileptiform discharges; case 2-improve localization of falsely generalized epileptic spasms; cases 3 and 4-improve localization of interictal epileptiform discharges in anatomic regions below the circumferential limit of standard low-density EEG coverage; case 5-improve noninvasive localization of the seizure onset zone in lesional epilepsy; cases 6 and 7-improve localization of the seizure onset zone to guide invasive investigation near eloquent cortex; case 8-identify epileptic fast oscillations; and case 9-map language cortex. Together, these nine cases illustrate that using both visual analysis and advanced techniques, HD-EEG can play an important role in clinical management.


Assuntos
Mapeamento Encefálico/métodos , Eletroencefalografia/métodos , Epilepsia/diagnóstico por imagem , Epilepsia/fisiopatologia , Adolescente , Adulto , Idoso , Mapeamento Encefálico/tendências , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiopatologia , Criança , Eletrodos/tendências , Eletroencefalografia/tendências , Feminino , Previsões , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Couro Cabeludo/diagnóstico por imagem , Couro Cabeludo/fisiopatologia , Convulsões/diagnóstico por imagem , Convulsões/fisiopatologia , Adulto Jovem
7.
BMJ Glob Health ; 6(2)2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33547175

RESUMO

BACKGROUND: We aimed to systematically identify, standardise and disseminate individual-level dietary intake surveys from up to 207 countries for 54 foods, beverages and nutrients, including subnational intakes by age, sex, education and urban/rural residence, from 1980 to 2015. METHODS: Between 2008-2011 and 2014-2020, the Global Dietary Database (GDD) project systematically searched for surveys assessing individual-level intake worldwide. We prioritised nationally or subnationally representative surveys using 24-hour recalls, Food-Frequency Questionnaires or short standardised questionnaires. Data were retrieved from websites or corresponding members as individual-level food group microdata or aggregate stratum-level data. Standardisation included quality assessment; data cleaning; categorising of foods and nutrients and their units; aggregation by demographic strata and energy adjustment. RESULTS: We standardised and incorporated 1220 surveys into the final GDD 2017 database, together represented 188 countries and 99.0% of the world's population in 2015. 72.1% were nationally, 17.0% subnationally, and 10.9% community-level representative. 41.2% used Food-Frequency Questionnaires; 23.4%, 24-hour recalls; 15.8%, Demographic Health Survey questionnaires; 13.1%, biomarkers and 6.4%, household surveys. 73.9% of surveys included data on children; 52.2%, by urban and rural residence; and 30.2%, by education. Most surveys were in high-income countries, followed by sub-Saharan Africa and Asia. Most commonly ascertained foods were fruits (N=803 surveys), non-starchy vegetables (N=787) and sugar-sweetened beverages (N=440); and nutrients, sodium (N=343), energy (N=256), calcium (N=224) and fibre (N=200). Least available data were on iodine, vitamin A, plant protein, selenium, added sugar and animal protein. CONCLUSIONS: This systematic search, retrieval and standardised effort provides the most comprehensive empirical evidence on dietary intakes across and within countries worldwide.


Assuntos
Bebidas , Dieta , Adulto , Animais , Criança , Humanos , Nutrientes , Inquéritos e Questionários , Verduras
8.
J Neurosci ; 41(8): 1816-1829, 2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33468567

RESUMO

Childhood epilepsy with centrotemporal spikes (CECTS) is the most common focal epilepsy syndrome, yet the cause of this disease remains unknown. Now recognized as a mild epileptic encephalopathy, children exhibit sleep-activated focal epileptiform discharges and cognitive difficulties during the active phase of the disease. The association between the abnormal electrophysiology and sleep suggests disruption to thalamocortical circuits. Thalamocortical circuit dysfunction resulting in pathologic epileptiform activity could hinder the production of sleep spindles, a brain rhythm essential for memory processes. Despite this pathophysiologic connection, the relationship between spindles and cognitive symptoms in epileptic encephalopathies has not been previously evaluated. A significant challenge limiting such work has been the poor performance of available automated spindle detection methods in the setting of sharp activities, such as epileptic spikes. Here, we validate a robust new method to accurately measure sleep spindles in patients with epilepsy. We then apply this detector to a prospective cohort of male and female children with CECTS with combined high-density EEGs during sleep and cognitive testing at varying time points of disease. We show that: (1) children have a transient, focal deficit in spindles during the symptomatic phase of disease; (2) spindle rate anticorrelates with spike rate; and (3) spindle rate, but not spike rate, predicts performance on cognitive tasks. These findings demonstrate focal thalamocortical circuit dysfunction and provide a pathophysiological explanation for the shared seizures and cognitive symptoms in CECTS. Further, this work identifies sleep spindles as a potential treatment target of cognitive dysfunction in this common epileptic encephalopathy.SIGNIFICANCE STATEMENT Childhood epilepsy with centrotemporal spikes is the most common idiopathic focal epilepsy syndrome, characterized by self-limited focal seizures and cognitive symptoms. Here, we provide the first evidence that focal thalamocortical circuit dysfunction underlies the shared seizures and cognitive dysfunction observed. In doing so, we identify sleep spindles as a mechanistic biomarker, and potential treatment target, of cognitive dysfunction in this common developmental epilepsy and provide a novel method to reliably quantify spindles in brain recordings from patients with epilepsy.


Assuntos
Córtex Cerebral/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Epilepsias Parciais/fisiopatologia , Sono/fisiologia , Tálamo/fisiopatologia , Adolescente , Criança , Pré-Escolar , Disfunção Cognitiva/etiologia , Eletroencefalografia , Epilepsias Parciais/complicações , Feminino , Humanos , Masculino , Vias Neurais/fisiopatologia
9.
Epilepsy Behav ; 103(Pt A): 106437, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31645314

RESUMO

OBJECTIVE: Childhood epilepsy with centrotemporal spikes (CECTS) (formally benign epilepsy with centrotemporal spikes, BECTS) is a common childhood epilepsy syndrome characterized by psychiatric, behavioral, and cognitive abnormalities and self-limited seizures. Although CECTS is one of the most well-characterized electroclinical epilepsy syndromes, the natural history of neuropsychiatric outcomes is poorly understood. We report the psychiatric, behavioral, and cognitive profiles over the course of disease from a large, prospectively-enrolled, longitudinal cohort of children with CECTS. We further characterize the detailed seizure course and test the relationship between several proposed risk factors and neuropsychiatric and seizure outcomes in these children. METHODS: Patients diagnosed with CECTS were enrolled as part of a community-based study and followed from diagnosis through disease resolution (16.0 ±â€¯3.1 years, N = 60). Twenty sibling controls were also recruited. We report the natural history of premorbid neuropsychiatric concerns, postmorbid neuropsychiatric diagnoses, long-term neuropsychological performance, seizure course, antiseizure medication (ASM) treatment response, and the relationship between duration seizure-free and remission. Age at onset and premorbid neuropsychiatric concerns were tested as predictors of seizure count, epilepsy duration, postmorbid neuropsychiatric diagnoses, and long-term neuropsychological performance. Antiseizure medication treatment duration, seizure count, and epilepsy duration were tested as predictors of postmorbid neuropsychiatric diagnoses and long-term neuropsychological performance. RESULTS: Children with CECTS had a high incidence of ADD/ADHD symptoms (18.3%) or learning difficulties (21.7%) before diagnosis. New or persistent ADHD (20%), mood disorders (23.6%), learning difficulties (14.5%), and behavioral disorders (7.3%) were common after CECTS diagnosis. At 9-year follow-up, performance on formal neuropsychological testing was comparable to population statistics and sibling controls. More than two-thirds of treated children experienced at least one seizure during treatment. Most children (61.7%) had entered terminal resolution after 12 months seizure-free. Among all children, for each month seizure-free, there was a 6-7% increase in the probability of achieving terminal remission (p < 1e-10). The presence of a premorbid neurodevelopmental concern predicted a longer epilepsy duration (p = 0.02), higher seizure count (p = 0.02), and a postmorbid psychiatric or neurodevelopmental diagnosis (p = 0.002). None of the tested features predicted long-term neuropsychological performance. SIGNIFICANCE: Children are at high risk of neuropsychiatric symptoms along the course of the disease in CECTS, however, long-term cognitive performance is favorable. The majority of children had a seizure while being treated with ASMs, suggesting that CECTS is not as pharmacoresponsive as assumed or that treatment approaches are not optimized. Among treated and untreated children, future seizure-risk can be estimated from duration seizure-free. The presence of a premorbid neuropsychiatric concern predicted a more severe disease course in CECTS.


Assuntos
Epilepsia Rolândica/fisiopatologia , Transtornos do Neurodesenvolvimento/fisiopatologia , Convulsões/fisiopatologia , Adolescente , Criança , Epilepsia Rolândica/complicações , Feminino , Seguimentos , Humanos , Masculino , Transtornos do Neurodesenvolvimento/etiologia , Convulsões/etiologia
10.
Epilepsia ; 60(12): 2508-2518, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31745988

RESUMO

OBJECTIVE: We evaluated the impact of monitoring indication, early electroencephalography (EEG), and clinical features on seizure risk in all neonates undergoing continuous EEG (cEEG) monitoring following a standardized monitoring protocol. METHODS: All cEEGs from unique neonates 34-48 weeks postmenstrual age monitored from 1/2011-10/2017 (n = 291) were included. We evaluated the impact of cEEG monitoring indication (acute neonatal encephalopathy [ANE], suspicious clinical events [SCEs], or other high-risk conditions [OHRs]), age, medication status, and early EEG abnormalities (including the presence of epileptiform discharges and abnormal background continuity, amplitude, asymmetry, asynchrony, excessive sharp transients, and burst suppression) on time to first seizure and overall seizure risk using Kaplan-Meier survival curves and multivariable Cox proportional hazards models. RESULTS: Seizures occurred in 28% of high-risk neonates. Discontinuation of monitoring after 24 hours of seizure-freedom would have missed 8.5% of neonates with seizures. Overall seizure risk was lower in neonates monitored for ANE compared to OHR (P = .004) and trended lower compared to SCE (P = .097). The time course of seizure presentation varied by group, where the probability of future seizure was less than 1% after 17 hours of seizure-free monitoring in the SCE group, but required 42 hours in the OHR group, and 73 hours in the ANE group. The presence of early epileptiform discharges increased seizure risk in each group (ANE: adjusted hazard ratio [aHR] 4.32, 95% confidence interval [CI] 1.23-15.13, P = .022; SCE: aHR 10.95, 95% CI 4.77-25.14, P < 1e-07; OHR: aHR 56.90, 95% CI 10.32-313.72, P < 1e-05). SIGNIFICANCE: Neonates who undergo cEEG are at high risk for seizures, and risk varies by monitoring indication and early EEG findings. Seizures are captured in nearly all neonates undergoing monitoring for SCE within 24 hours of cEEG monitoring. Neonates monitored for OHR and ANE can present with delayed seizures and require longer durations of monitoring. Early epileptiform discharges are the best early EEG feature to predict seizure risk.


Assuntos
Eletroencefalografia/tendências , Convulsões/diagnóstico , Convulsões/fisiopatologia , Eletroencefalografia/métodos , Feminino , Humanos , Recém-Nascido , Masculino , Valor Preditivo dos Testes , Fatores de Risco
11.
Brain Commun ; 1(1): fcz002, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31608323

RESUMO

Benign epilepsy with centrotemporal spikes is a common childhood epilepsy syndrome that predominantly affects boys, characterized by self-limited focal seizures arising from the perirolandic cortex and fine motor abnormalities. Concurrent with the age-specific presentation of this syndrome, the brain undergoes a developmentally choreographed sequence of white matter microstructural changes, including maturation of association u-fibres abutting the cortex. These short fibres mediate local cortico-cortical communication and provide an age-sensitive structural substrate that could support a focal disease process. To test this hypothesis, we evaluated the microstructural properties of superficial white matter in regions corresponding to u-fibres underlying the perirolandic seizure onset zone in children with this epilepsy syndrome compared with healthy controls. To verify the spatial specificity of these features, we characterized global superficial and deep white matter properties. We further evaluated the characteristics of the perirolandic white matter in relation to performance on a fine motor task, gender and abnormalities observed on EEG. Children with benign epilepsy with centrotemporal spikes (n = 20) and healthy controls (n = 14) underwent multimodal testing with high-resolution MRI including diffusion tensor imaging sequences, sleep EEG recordings and fine motor assessment. We compared white matter microstructural characteristics (axial, radial and mean diffusivity, and fractional anisotropy) between groups in each region. We found distinct abnormalities corresponding to the perirolandic u-fibre region, with increased axial, radial and mean diffusivity and fractional anisotropy values in children with epilepsy (P = 0.039, P = 0.035, P = 0.042 and P = 0.017, respectively). Increased fractional anisotropy in this region, consistent with decreased integrity of crossing sensorimotor u-fibres, correlated with inferior fine motor performance (P = 0.029). There were gender-specific differences in white matter microstructure in the perirolandic region; males and females with epilepsy and healthy males had higher diffusion and fractional anisotropy values than healthy females (P ≤ 0.035 for all measures), suggesting that typical patterns of white matter development disproportionately predispose boys to this developmental epilepsy syndrome. Perirolandic white matter microstructure showed no relationship to epilepsy duration, duration seizure free, or epileptiform burden. There were no group differences in diffusivity or fractional anisotropy in superficial white matter outside of the perirolandic region. Children with epilepsy had increased radial diffusivity (P = 0.022) and decreased fractional anisotropy (P = 0.027) in deep white matter, consistent with a global delay in white matter maturation. These data provide evidence that atypical maturation of white matter microstructure is a basic feature in benign epilepsy with centrotemporal spikes and may contribute to the epilepsy, male predisposition and clinical comorbidities observed in this disorder.

12.
Brain ; 142(5): 1296-1309, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30907404

RESUMO

In the past decade, brief bursts of fast oscillations in the ripple range have been identified in the scalp EEG as a promising non-invasive biomarker for epilepsy. However, investigation and clinical application of this biomarker have been limited because standard approaches to identify these brief, low amplitude events are difficult, time consuming, and subjective. Recent studies have demonstrated that ripples co-occurring with epileptiform discharges ('spike ripple events') are easier to detect than ripples alone and have greater pathological significance. Here, we used objective techniques to quantify spike ripples and test whether this biomarker predicts seizure risk in childhood epilepsy. We evaluated spike ripples in scalp EEG recordings from a prospective cohort of children with a self-limited epilepsy syndrome, benign epilepsy with centrotemporal spikes, and healthy control children. We compared the rate of spike ripples between children with epilepsy and healthy controls, and between children with epilepsy during periods of active disease (active, within 1 year of seizure) and after a period of sustained seizure-freedom (seizure-free, >1 year without seizure), using semi-automated and automated detection techniques. Spike ripple rate was higher in subjects with active epilepsy compared to healthy controls (P = 0.0018) or subjects with epilepsy who were seizure-free ON or OFF medication (P = 0.0018). Among epilepsy subjects with spike ripples, each month seizure-free decreased the odds of a spike ripple by a factor of 0.66 [95% confidence interval (0.47, 0.91), P = 0.021]. Comparing the diagnostic accuracy of the presence of at least one spike ripple versus a classic spike event to identify group, we found comparable sensitivity and negative predictive value, but greater specificity and positive predictive value of spike ripples compared to spikes (P = 0.016 and P = 0.006, respectively). We found qualitatively consistent results using a fully automated spike ripple detector, including comparison with an automated spike detector. We conclude that scalp spike ripple events identify disease and track with seizure risk in this epilepsy population, using both semi-automated and fully automated detection methods, and that this biomarker outperforms analysis of spikes alone in categorizing seizure risk. These data provide evidence that spike ripples are a specific non-invasive biomarker for seizure risk in benign epilepsy with centrotemporal spikes and support future work to evaluate the utility of this biomarker to guide medication trials and tapers in these children and predict seizure risk in other at-risk populations.


Assuntos
Potenciais de Ação/fisiologia , Eletroencefalografia/métodos , Epilepsia Rolândica/fisiopatologia , Couro Cabeludo/fisiopatologia , Convulsões/fisiopatologia , Adolescente , Criança , Pré-Escolar , Epilepsia Rolândica/diagnóstico , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Fatores de Risco , Convulsões/diagnóstico
13.
Brain Behav ; 9(3): e01237, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30790472

RESUMO

INTRODUCTION: Benign epilepsy with centrotemporal spikes (BECTS) is a common form of childhood epilepsy with the majority of those afflicted remitting during their early teenage years. Seizures arise from the lower half of the sensorimotor cortex of the brain (e.g. seizure onset zone) and the abnormal epileptiform discharges observed increase during NREM sleep. To date no clinical factors reliably predict disease course, making determination of ongoing seizure risk a significant challenge. Prior work in BECTS have shown abnormalities in beta band (14.9-30 Hz) oscillations during movement and rest. Oscillations in this frequency band are modulated by state of consciousness and thought to reflect intrinsic inhibitory mechanisms. METHODS: We used high density EEG and source localization techniques to examine beta band activity in the seizure onset zone (sensorimotor cortex) in a prospective cohort of children with BECTS and healthy controls during sleep. We hypothesized that beta power in the sensorimotor cortex would be different between patients and healthy controls, and that beta abnormalities would improve with resolution of disease in this self-limited epilepsy syndrome. We further explored the specificity of our findings and correlation with clinical features. Statistical testing was performed using logistic and standard linear regression models. RESULTS: We found that beta band power in the seizure onset zone is different between healthy controls and BECTS patients. We also found that a longer duration of time spent seizure-free (corresponding to disease remission) correlates with lower beta power in the seizure onset zone. Exploratory spatial analysis suggests this effect is not restricted to the sensorimotor cortex. Exploratory frequency analysis suggests that this phenomenon is also observed in alpha and gamma range activity. We found no relationship between beta power and the presence or rate of epileptiform discharges in the sensorimotor cortex or a test of sensorimotor performance. CONCLUSION: These results provide evidence that cortical beta power in the seizure onset zone may provide a dynamic physiological biomarker of disease in BECTS.


Assuntos
Eletroencefalografia/métodos , Epilepsia Rolândica , Convulsões/diagnóstico , Córtex Sensório-Motor , Adolescente , Criança , Epilepsia Rolândica/diagnóstico , Epilepsia Rolândica/fisiopatologia , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco/métodos , Córtex Sensório-Motor/diagnóstico por imagem , Córtex Sensório-Motor/fisiopatologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA